Joyce O’Shaughnessy, MD: Before we get to the new olaparib data, let’s talk a little about a struggle that we all have in day-to-day practice. You’ve got a germline BRCA patient, but she’s in the curative setting. Let’s put her in the preoperative setting. She can either be triple-negative, or she could be ER-positive. Do you treat her any differently today, based on what we know with regard to how you’d give her preoperative therapy? How about you, Tiffany? What do you do in your practice?

Tiffany Traina, MD: This is a perfect opportunity, on the heels of OlympiAD, to pursue accrual to OlympiA, which is an adjuvant study for olaparib in patients who are non–BRCA-mutant to see whether there’s potential benefit with the addition of olaparib following standard-of-care adjuvant therapy.

I think that the neoadjuvant approach is a really compelling one because we can enrich for response to therapy and know who may potentially need additional treatment after surgery. We know that we can downstage the axillary nodes. With preoperative therapy, we’re allowing our patients to have less morbidity from their surgery choice. So I think that the neoadjuvant setting is really a rich one. I don’t know, however, that it necessarily changes the backbone regimen of chemotherapy that I’m offering.

Joyce O’Shaughnessy, MD: Do you use much in the way of platinums, up front, or do you wait to see what the pathologic response is before considering an adjuvant platinum, in the BRCAs, in particular?

Tiffany Traina, MD: In the germline?

Joyce O’Shaughnessy, MD: Yes, in the germline.

Tiffany Traina, MD: In the germline setting, it’s unclear whether platinum has really added anything. These are often women who are having a risk-reducing mastectomy at the time of surgery. I would certainly consider it for the opportunity to downstage the axillary nodes, but it’s really a multidisciplinary discussion about whether the platinum is necessary or not.

Joyce O’Shaughnessy, MD: About how much you really have to get cytoreduction of that before their surgery and such.

Tiffany Traina, MD: Correct.

Joyce O’Shaughnessy, MD: How about you, Nadine? What are you doing with the BRCA1 and BRCA2 germline BRCA patients who have early-stage disease?

Nadine Tung, MD: I am doing the same thing. I’m not really changing the chemotherapy that I give. It’s nice to know whether the platinum’s an inactive agent. Again, most of our data are in the triple-negative and BRCA1 settings. Certainly, if I’m concerned about an anthracycline (AC) for somebody who has a contraindication, I’m very comfortable using a platinum-based regimen. That’s nice to know. Otherwise, despite what I just said for GeparSixto, if I’m starting with an AC in a triple-negative patient, and I’m not getting the response that I want, or if there’s still significant disease, I’m probably going to add the carboplatin, weekly, with the taxane. But you often get very, very good responses with standard therapy.

Joyce O’Shaughnessy, MD: So you’ll flex it?

Nadine Tung, MD: Absolutely.

Joyce O’Shaughnessy, MD: If they have a clinical complete response, real fast, you won’t, necessarily. GeparSixto is quite interesting. With the CALGB trial that also looked at the plus/minus platinum, hopefully we’ll be able to look at a BRCA cohort, and hopefully it will tell the same story. So we’ll have some clear guidance there. I do the same thing. If somebody comes in with a huge amount of disease, it’s really going to be a difficult operation. I’ll start with AC and then go on to paclitaxel/carboplatin. Or, if they do really well with standard therapy and aren’t at a pathologic complete response, if they have germline BRCA, I will give the capecitabine, per CREATE-X, afterward.

But I have found good safety in adding 4 cycles of carboplatin and then finishing up the 6 months of the capecitabine. So I often flex it too. I’m still sort of adding it on in the highest-risk population, just because we don’t know yet. We have the NSABP randomized trial, but that’s not testing germline BRCA patients. But at least we’re going to find out what platinum really does, overall. We just don’t have super-great data yet on disease-free survival, particularly in the BRCA population.

Nadine Tung, MD: We’re waiting on data from the CALGB 40603 trial. We have data from the I-SPY trial, as well as the BrighTNess study, which was just published. It was sort of similar. They used the taxane versus AC weekly Taxol, and they added either carboplatin or carboplatin/veliparib. If you look at that paper (I think they had 93 BRCA carriers), it’s sort of a similar story. The benefit didn’t look quite as large with the addition of the carboplatin. The benefit was sort of none with the veliparib, as it was in the non-BRCA carriers. Again, these were triple-negative breast cancer patients. So I think there are a few lines of evidence. They’re so chemo-sensitive that the standard therapy is good.

Joyce O’Shaughnessy, MD: Yes. Interesting. It’s not what we expected. It’s not that we thought the platinum was going to hit it out of the park for the BRCAs, but they do well, in general, with chemotherapy. Maybe platinum is just not that non–cross-resistant to an AC-type regimen?

Nadine Tung, MD: Well, I think there’s a different argument to be made for substituting, but we don’t have that data yet.

Transcript Edited for Clarity

SELECTEDLANGUAGE

Transcript:

Joyce O’Shaughnessy, MD: Before we get to the new olaparib data, let’s talk a little about a struggle that we all have in day-to-day practice. You’ve got a germline BRCA patient, but she’s in the curative setting. Let’s put her in the preoperative setting. She can either be triple-negative, or she could be ER-positive. Do you treat her any differently today, based on what we know with regard to how you’d give her preoperative therapy? How about you, Tiffany? What do you do in your practice?

Tiffany Traina, MD: This is a perfect opportunity, on the heels of OlympiAD, to pursue accrual to OlympiA, which is an adjuvant study for olaparib in patients who are non–BRCA-mutant to see whether there’s potential benefit with the addition of olaparib following standard-of-care adjuvant therapy.

I think that the neoadjuvant approach is a really compelling one because we can enrich for response to therapy and know who may potentially need additional treatment after surgery. We know that we can downstage the axillary nodes. With preoperative therapy, we’re allowing our patients to have less morbidity from their surgery choice. So I think that the neoadjuvant setting is really a rich one. I don’t know, however, that it necessarily changes the backbone regimen of chemotherapy that I’m offering.

Joyce O’Shaughnessy, MD: Do you use much in the way of platinums, up front, or do you wait to see what the pathologic response is before considering an adjuvant platinum, in the BRCAs, in particular?

Tiffany Traina, MD: In the germline?

Joyce O’Shaughnessy, MD: Yes, in the germline.

Tiffany Traina, MD: In the germline setting, it’s unclear whether platinum has really added anything. These are often women who are having a risk-reducing mastectomy at the time of surgery. I would certainly consider it for the opportunity to downstage the axillary nodes, but it’s really a multidisciplinary discussion about whether the platinum is necessary or not.

Joyce O’Shaughnessy, MD: About how much you really have to get cytoreduction of that before their surgery and such.

Tiffany Traina, MD: Correct.

Joyce O’Shaughnessy, MD: How about you, Nadine? What are you doing with the BRCA1 and BRCA2 germline BRCA patients who have early-stage disease?

Nadine Tung, MD: I am doing the same thing. I’m not really changing the chemotherapy that I give. It’s nice to know whether the platinum’s an inactive agent. Again, most of our data are in the triple-negative and BRCA1 settings. Certainly, if I’m concerned about an anthracycline (AC) for somebody who has a contraindication, I’m very comfortable using a platinum-based regimen. That’s nice to know. Otherwise, despite what I just said for GeparSixto, if I’m starting with an AC in a triple-negative patient, and I’m not getting the response that I want, or if there’s still significant disease, I’m probably going to add the carboplatin, weekly, with the taxane. But you often get very, very good responses with standard therapy.

Joyce O’Shaughnessy, MD: So you’ll flex it?

Nadine Tung, MD: Absolutely.

Joyce O’Shaughnessy, MD: If they have a clinical complete response, real fast, you won’t, necessarily. GeparSixto is quite interesting. With the CALGB trial that also looked at the plus/minus platinum, hopefully we’ll be able to look at a BRCA cohort, and hopefully it will tell the same story. So we’ll have some clear guidance there. I do the same thing. If somebody comes in with a huge amount of disease, it’s really going to be a difficult operation. I’ll start with AC and then go on to paclitaxel/carboplatin. Or, if they do really well with standard therapy and aren’t at a pathologic complete response, if they have germline BRCA, I will give the capecitabine, per CREATE-X, afterward.

But I have found good safety in adding 4 cycles of carboplatin and then finishing up the 6 months of the capecitabine. So I often flex it too. I’m still sort of adding it on in the highest-risk population, just because we don’t know yet. We have the NSABP randomized trial, but that’s not testing germline BRCA patients. But at least we’re going to find out what platinum really does, overall. We just don’t have super-great data yet on disease-free survival, particularly in the BRCA population.

Nadine Tung, MD: We’re waiting on data from the CALGB 40603 trial. We have data from the I-SPY trial, as well as the BrighTNess study, which was just published. It was sort of similar. They used the taxane versus AC weekly Taxol, and they added either carboplatin or carboplatin/veliparib. If you look at that paper (I think they had 93 BRCA carriers), it’s sort of a similar story. The benefit didn’t look quite as large with the addition of the carboplatin. The benefit was sort of none with the veliparib, as it was in the non-BRCA carriers. Again, these were triple-negative breast cancer patients. So I think there are a few lines of evidence. They’re so chemo-sensitive that the standard therapy is good.

Joyce O’Shaughnessy, MD: Yes. Interesting. It’s not what we expected. It’s not that we thought the platinum was going to hit it out of the park for the BRCAs, but they do well, in general, with chemotherapy. Maybe platinum is just not that non–cross-resistant to an AC-type regimen?

Nadine Tung, MD: Well, I think there’s a different argument to be made for substituting, but we don’t have that data yet.